PMID- 31698409
OWN - NLM
STAT- MEDLINE
DCOM- 20201228
LR  - 20231113
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 45
IP  - 3
DP  - 2020 Feb
TI  - Blocking CRH receptors in adults mitigates age-related memory impairments 
      provoked by early-life adversity.
PG  - 515-523
LID - 10.1038/s41386-019-0562-x [doi]
AB  - In humans, early-life adversity is associated with impairments in learning and 
      memory that may emerge later in life. In rodent models, early-life adversity 
      directly impacts hippocampal neuron structure and connectivity with progressive 
      deficits in long-term potentiation and spatial memory function. Previous work has 
      demonstrated that augmented release and actions of the stress-activated 
      neuropeptide, CRH, contribute to the deleterious effects of early-life adversity 
      on hippocampal dendritic arborization, synapse number and memory-function. 
      Early-life adversity increases hippocampal CRH expression, and blocking 
      hippocampal CRH receptor type-1 (CRHR1) immediately following early-life 
      adversity prevented the consequent memory and LTP defects. Here, we tested if 
      blocking CRHR1 in young adults ameliorates early-life adversity-provoked memory 
      deficits later in life. A weeklong course of a CRHR1 antagonist in 2-month-old 
      male rats prevented early-life adversity-induced deficits in object recognition 
      memory that emerged by 12 months of age. Surprisingly, whereas the intervention 
      did not mitigate early-life adversity-induced spatial memory losses at 4 and 8 
      months, it restored hippocampus-dependent location memory in 12-month-old rats 
      that experienced early-life adversity. Neither early-life adversity nor CRHR1 
      blockade in the adult influenced anxiety- or depression-related behaviors. 
      Altogether, these findings suggest that cognitive deficits attributable to 
      adversity during early-life-sensitive periods are at least partially amenable to 
      interventions later in life.
FAU - Short, Annabel K
AU  - Short AK
AUID- ORCID: 0000-0001-9654-3197
AD  - Department of Anatomy and Neurobiology, University of California- Irvine, Irvine, 
      CA, USA. akshort@uci.edu.
AD  - Department of Pediatrics, University of California-Irvine, Irvine, CA, USA. 
      akshort@uci.edu.
FAU - Maras, Pamela M
AU  - Maras PM
AD  - Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Pham, Aidan L
AU  - Pham AL
AD  - Department of Anatomy and Neurobiology, University of California- Irvine, Irvine, 
      CA, USA.
AD  - Department of Pediatrics, University of California-Irvine, Irvine, CA, USA.
FAU - Ivy, Autumn S
AU  - Ivy AS
AUID- ORCID: 0000-0003-1775-6253
AD  - Department of Anatomy and Neurobiology, University of California- Irvine, Irvine, 
      CA, USA.
AD  - Department of Pediatrics, University of California-Irvine, Irvine, CA, USA.
FAU - Baram, Tallie Z
AU  - Baram TZ
AUID- ORCID: 0000-0003-0771-8616
AD  - Department of Anatomy and Neurobiology, University of California- Irvine, Irvine, 
      CA, USA.
AD  - Department of Pediatrics, University of California-Irvine, Irvine, CA, USA.
AD  - Department of Neurology, University of California-Irvine, Irvine, CA, USA.
LA  - eng
GR  - R01 MH073136/MH/NIMH NIH HHS/United States
GR  - R01 NS028912/NS/NINDS NIH HHS/United States
GR  - P50 MH096889/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191107
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Pyrimidines)
RN  - 0 (R 121919)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 5CLY6W2H1M (CRF receptor type 1)
SB  - IM
MH  - Age Factors
MH  - Aging/drug effects/physiology/*psychology
MH  - Animals
MH  - Animals, Newborn
MH  - Female
MH  - Injections, Intraventricular
MH  - Male
MH  - Memory Disorders/etiology/*prevention & control/*psychology
MH  - Pregnancy
MH  - Pyrimidines/administration & dosage
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Corticotropin-Releasing Hormone/*antagonists & inhibitors/physiology
MH  - Stress, Psychological/complications/*drug therapy/*psychology
PMC - PMC6969076
EDAT- 2019/11/08 06:00
MHDA- 2020/12/29 06:00
PMCR- 2021/02/01
CRDT- 2019/11/08 06:00
PHST- 2019/08/21 00:00 [received]
PHST- 2019/10/28 00:00 [accepted]
PHST- 2019/10/26 00:00 [revised]
PHST- 2019/11/08 06:00 [pubmed]
PHST- 2020/12/29 06:00 [medline]
PHST- 2019/11/08 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.1038/s41386-019-0562-x [pii]
AID - 562 [pii]
AID - 10.1038/s41386-019-0562-x [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2020 Feb;45(3):515-523. doi: 10.1038/s41386-019-0562-x. 
      Epub 2019 Nov 7.